Control of nematodes with phosphorodiamidothioates



United States Patent Int. Cl. A0ln 9/36 US. Cl. 424220 4 Claims ABSTRACT OF THE DISCLOSURE 'Nematocidal phosphoroamidothioates of the formula:

6 (RRN)mISR (ones wherein R, R and R each independently represents a group of l to 12 carbon atoms selected from alkyl, alkenyl, chloro'alkyl, or bromoalkyl; R :R, R R cycloalkyl and alkynyl of up to 12. carbon atoms; m=2 when 21:0 and m=l when 11:1, are described. Some of these compounds are novel.

This is a division of application Ser. No. 522,046, filed Jan. 21, 1966, now US. Pat. 3,454,682.

This invention relates to a novel method for protect ing plants from attack by nematodes. According to this invention such protection is effected by treating the soil in which the plants are grown or by treating the plants directly. The invention in particular relates to certain phosphoroamidothioates and phosphorodiamidothioates useful to protect plants from nematode attack. It also relates to certain phosphorodiamidothioates which are novel compositions of matter.

To control root infesting nematodes with conventional nematocides the farmer generally has to apply large quantities of the active ingredient per acre. Quantities up to 20 gallons per acre are frequently required for nematode control. Use of such large quantities requires specialized application equipment. Most of the currently employed chemicals such as ethylene dibromide, chloropicrin, and 1,3-dichloropropene are highly volatile and require proper placement in the soil. In addition many of the commercial nematocides are quite phytotoxic and the treated soil must be aerated for extended periods of time prior to planting. In general due to the large quantities of the active pesticide required, the specialized equipment required, and the need to aerate the soil prior to planting, the use of many commercial nematocides has been restricted to a limited number of crops of high value.

It is an object of the present invention to provide a method of controlling nematodes in soil, such method providing residual effectiveness. By residual effectiveness is meant the provision of protection for the growing crop for the duration of its maturation. It is a further object of the method of the invention to provide a class of compounds which will effectively control these plant pests and yet not injure or adversely affect the growing plant. Another object of the invention is to provide a useful class of nematocides which are novel composi tions of matter.

Still further objects and the scope of applicability of the invention will become apparent from the description and specific examples which follow.

The objects of the invention are accomplished by the Patented Nov. 3, 1970 use of nematocidally effective amounts of phosphoroamidothioates of the following formula:

(OBS-i wheren R, R R and R each independently represent a group of up to 12. carbon atoms consisting of alkyl, alkenyl, chloro'alkyl or bromoalkyl and R in addition may also represent cycloalkyl or alkynyl; m =l or 2 and when 111:2, 11:0 and when m=1, n=l.

Typical examples of compounds which are employed according to the invention in addition to those given in the working examples include:

N,N-dimethyl O-ethyl S-ethyl phosphoroamidothicate N,N-dimethyl O-isopropyl S-methyl phosphoroamidothioate N,N-dimethyl O-propy1 S-ethyl phosphoroamidothioate N,N-dimethyl O-propyl S-butyl phosphoroamidothioate N,N-dimethyl O-methyl S-hexyl phosphoroamidothioate N,N-dimethyl O-ethyl S-hexyl phosphoroamidothioate N,N-dimethyl O-ethyl S-cyclohexyl phosphoroamidothioate N,N-dimethyl O-ethyl S-octyl phosphoroamidothioate N,N-diethyl O-methyl S-butyl phosphoroamidothioate N,N-diethyl O-methyl S-hexyl phosphoroamidothioate N,N-diethyl O-methyl S-nonyl phosphoroamidothioate N,N-diallyl O-ethyl S-hexyl phosphoroamidothioate N,Ndiallyl O-ethyl S-decyl phosphoroamidothioate N,N,N,N-tetramethyl S-methyl phosphorodiamidothioate N,N,N,N-tetramethyl S-ethyl phosphorodiamidothioate N,-N,N,N-tetramethyl S-decyl phosphorodiamidothioate N,N,N,N-tetramethyl S-dodecyl phosphorodiamidothioate N,N,N',N-tetramethyl S-allyl phosphorodiamidothioate N,N,N',N-tetrarnethyl S-(2-propynyl) phosphorodiamidothioate N,N,N,N'-tetramethyl S-(Z-butenyl) phosphorodiamidothioate N,N,N,-N'-tetraethyl S-propyl phosphorodiamidothicate N,N,N',N'-tetraethyl S-octyl phosphorodiamidothicate The compounds of the following formula comprise a preferred class of compounds according to the invention because of their effectiveness as residual nematocides.

(RR N)zl -SR (II) wherein R, R and R have the meaning hereinbefore specified. Such active nematocides are typified in working Examples Ill and IV.

A preferred subclass of the compounds used according to the invention are those members of Formula II wherein R and R represent alkyl of l to 4 carbon atoms. Such compounds are preferred because of their excellent nematocidal properties. Such compounds have exhibited high toxicity against nematodes attacking the roots of a Wide variety of economically important crops. These c0mpounds are effective nematocides when applied to the soil and yet at effective dosages will not adversely affect the growing plant.

The discovery of a novel class of effective nematocidal phosphorodiamidothioates is a further embodiment of the invention. Such compounds have been found to be highly active in in vitro screening tests and as well in trials wherein the compound was incorporated into nematode-infested soil. These phosphorodiamidothioates are characterized by the formula:

wherein R is alkyl of 1 to 4 carbon atoms and R represents alkyl, cycloalkyl, monochloroalkyl or alkynyl of up to 12 carbon atoms. Such novel compounds of this class include for example:

N,N,N',N-tetramethyl S-methyl phosphorodiamidothioate N,N,N',N'-tetramethyl S-ethyl phosphorodiamidothioate N.N,N,N'-tetramethyl S-propyl phosphorodiamidothioate N,N,N',N'-tetramethyl S-isopropyl phosphorodiamidothioate 1 thioate N,N,N,N-tetraisopropyl S-butyl phosphorodiamidothioate N,N,N',N-tetrabutyl S-methyl phosphorodiamidothioate N,N,N,N-tetrabutyl S-ethyl phosphorodiamidothioate A particularly preferred subclass of these phosphorodiamidothioates are those members of Formula III where R represents methyl. Such compounds are preferred because of their high activity towards soil-borne nematodes and their residual properties in the soil.

The novel compound, N,N,N,N-tetramethyl S-butyl phosphorodiamidothioate, is an especially preferred member of the class because of its outstanding performance in the laboratory and in the field as an effective nematocide. Furthermore this compound has exhibited a high 40 degree of toxicity to certain soil insect pests.

An essential feature of the configuration of the compounds used according to the invention is the thio linkage to the phosphorus atom. It has been found that phosphoroamidothioates and phosphorodiamidothioates are highly eifective nematocides while the corresponding phosphoroamidates and phosphorodiamidates do not possess such high activity against root parasitic nematodes in soil tests. Further the amidothioates and diamidothioates exhibit the unusual property of combined effectiveness against soil 5O dwelling parasitic nematodes and root-feeding insects.

The phosphoroamidothioates and phosphorodiamidothioates of the invention are in general oily liquids, light yellow to brownish in color, having boiling points in the range of approximately C. at 0.1 torr to approxi- 55 mately 150 C. at 6.5 torr. They are moderately soluble in most organic solvents such as methanol, ethanol, isopropanol, acetone and xylene.

The phosphoroamidothioates of the invention are readily prepared by reaction of the appropriate phosphoro- 6Q amidite, (RR N)P(OR or (RR N) P(OR), with phosphorodiamidite, the appropriate thiocyanate,

4 R SCN, the reaction proceeding according to the equation:

(RR N)m-IlOR R SON R CN(about 90-95% The reactions in general are exothermic, and may be carried out with or without solvents by mixing the reactants and heating, if necessary, to initiate the reaction. The products, high boiling liquids, are readily recovered and purified by distillation at very low pressures. If desired, the reaction may be moderated by inclusion of an inert solvent, aromatic liquids such as benzene, xylene, toluene being suitable for the purpose. The reaction is satisfactorily carried out by using about stoichiometric (mole/mole) proportions of the reactants.

The thiocyanate intermediates are known compounds, prepared by alkylation of an aqueous solution of KSCN or by boiling an alcoholic solution of KSCN with an alkyl bromide (about 1.1:1 mole ratio).

The phosphoroamidites can be prepared by reacting at from about 30 C. to 50 C., the appropriate alcohol and phosphorus trichloride to form the phosphorodichloridite. The product is then reacted further with alcohol in the presence of a tertiary amine base to form the phosphorochloridite, which is reacted with the appropriate amine (2 moles of amine per mole of phosphorochloridite) to form the desired phosphoramidite. The desired phosphorodiamidite is prepared in a similar manner by reacting the phosphorodichloridite with the amine (1:2 mole ratio), using ether or pentane as solvent.

The following examples are presented to illustrate typical preparations of compounds of the invention and to illustrate the biological effectiveness of selected compounds of the invention. The scope of the invention should not be regarded as being limited by the following illustrative examples.

EXAMPLE I Preparation of N,N,N,N'-tetramethyl S-butyl phosphorodiamidothioate n-Butyl thiocyanate (5.7 g., 0.05 m.) was added dropwise with stirring to ethyl N,N,N',N-tetramethylphosphorodiamidite (8.2 g., 0.05 m.) preheated to 40 C. The temperature rose spontaneously to 160 C. The mixture was allowed to cool and then Claisen distilled in vacuo to give 11.0 g. (96% yield) of N,N,N,N-tetramethyl S-butyl phosphorodiamidothioate as a colorless liquid boiling at 91 C. at 0.1 mm. Hg, 11 1.5315. The struc ture was confirmed by infrared spectrum and elemental analysis.

Analysis.Calcd. for PN SOC H (percent): P, 13.85; N, 12.5; S, 14.3. Found (percent): P, 14.1; N, 11.6; S, 14.5.

In addition the following table summarizes the experimental data obtained in the preparation of related exemplary S-esters of N,N,N,N-tetramethyl phosphorodiamidothioic acid:

P analysis St t B T t IIndgx of Yield,

ar mg 01 mg p re rac ion, per- Cale. Found S-estor temp, 0. C./torr 1111 cent percent, w. percent, w.

S-methyl 0 63/0. 01 1.4945 66 17 0 17 3 S-ethy1- 0 76/03 1 4910 72 15.8 16.1 S-hexyl- 20 98/0. 08 1.4839 79 12. 3 12. 0 S eyclohexyl 90 106/0. 09 1. 5096 88 12. 4 12.3 ecy1 136/0. 06 1. 4793 90 10. 1 10. 1 S-propyl 25 69-71/0. 01 87 N-13. 3 N -13. 3 S-sec-butyl 10 62-71/0. 15 49 13. 8 14. 2 S-1sopr0py1 25 106-111/6. 3 35 14. 8 15. 3 S-(3-cl1loropropyl) .1 15 111-113/0. l 28 12. 7 ll. 7

EXAMPLE II 1? analysis Index of Yield, Starting Boiling pt. retraction, per- Cale, Found, S-ester temp, 0. Qltori' 119 percent, w. percent, w.

S-ethyl 20 76/0 1 1. 4792 75 1G. 9 16. 5 S-butyl. 40 86/0. 1 1. 4750 74 14. 7 14. 5 S-0cty1 110 120 0. 1 1. 4720 75 ll. 0 10.8 shawl" 110 12s-30/0.0s 1. 4720 88 10.5 9.5

EXAMPLE III 20 Nematocide tests--water screen diisqpropyl o'ethyl s'dodecyl Phosphoro' amidothioate 76 I11 this test, thfi tfiSt COIIIP llIld at p.p.m. 1S 8118- N,N O methyl Sqmethyl phosphoropended in water containing 0.05 per by w i f amidothioate 100 nonylphcnyl polyeth xy ethanOl (TIiOIl X400) emulsi- N,N diallyl O methyl S-butyl phosphoroar. The test solution is inoculated with root-knot nem midothioate 93 todes, Me'loidogyne incognita (Var. acrita), which are eX- N N di 11 1 O-ethy] s-d 1 h h id osed to the test solution for 24 hours. The mort lity thioate 59 of the nematode larvae is obtained by transferring the N,N,NQN' tetramethyl S- 1 PhOSPhOmtreated larvae to nematode-free soil and seeding the soil diamidothioate 93 with tomatoes which are indicator plants for root-knot N,N,N',N' tetramethyl S (2- 1 h infection. The percent control is Obtained by c mp r phorodiamidothioate 57 son of the root infection of the treated larvae with soil N,N,N'Jq' t th l S isopropyl Phosinoculated with untreated larvae. The results o t ined r phorodiamidothioate 43 summarized in Table I. N,N,N,N' tetramethyl S butyl phosphorodiamidothioate 80 TABLE I N,N,N',N' tetramethyl S-sec-butyl phosphoro- Control of root-knot nemat de-w er screen diamidothioate 79 Compound: Percent control at 1000 ppm. 40 ,N,-- tetramethyl -p y Phosphoro- N,N dimethyl O methyl S-ethyl phosphorodlamldothloate 86 amidothioate 5O r me hyl S (3 chloropropyl) N,N dimethyl O-ethyl S-methyl phosphorophosphorodiamidothioate 100 amidothioate 100 g g r hyl S butyl phosphorodiimeth IO-iso r0 1 S-meth l hos horo- 0t loflte 100 2 l I11 l dOthlO ;1t6 "if? i 50 ZN' Y1 S cyclohexyl phos- N,N dimethyl O-methyl S-butyl phosphorophorodlamldothioate 100 amidothioate 100 'J tetr ethyl S octyl phosphorodi- N,N-dimethyl O-ethyl S-butyl hos horoamidohioate 79 thioate 1 tet aethyl S nonyl phosphorodidimethyl O-propyl S-hexyl phosphoroamidothioate 93 amidothioate 1001 ,N'N' tetraethyl S-dOdlecyl phosphorodi- N,N dimethyl 0 ethyl S-heptyl phospor amidothioate 50 amidothioate 100 N,N,N'N' tetraisopropyl S-methyl phosphoro- N,N dimethyl O-is0pr0Pyl W P P diamidothioate 100 amidothioate 64 N,N-dimethyl O-ethyl S-decyl phosphoroamido- 92 EXAMPLE IV thioate N,N dimethyl O-ethyl S-dodecyl phosphoro- Nematoclde tests so1l mlx amidothioate 100 The compounds of the invention were thoroughly mixed N,N diethvl Y s-butyl phosphoroamldowith soil infested with the root-knot nematode, thioate 100 Meloidogyne incognita (Var. acrita). All tests were made N,N lw methyl s'cyclohexyl phos' in duplicate. In addition two-quart jars of untreated soil phoroilmldothloate 83 served as controls. The samples of soil were held at g i 3 52 3 3 methyl s'heptyl phosphoro' 91 6 80 F. for two and four weeks, then were transferred to ""7"" 4-inch plant pots and seeded with tomatoes. Tomatoes gi gs O'ethyl f i 100 are excellent indicator plants for. evaluation of the pres- NN g 'fg gg i' hg phosphoro ence of root-knot nematodes in the soil. After two and amidothioate 79 four weeks, the soil was washed from the roots of the NN diisopropyl O ethy1 S ethy1 phosphoro plants and the number of root-knot galls, as evidence of amidothioate 100 the feeding of nematodes, was visually ascertained by N,N diisopropyl O-methyl S-butyl phosphoroexperienced observers. The dosages used and the control amidothioate 83 of nematodes obtained at each dosage of each of the test N,N diisopropyl O-ethyl S-cyclohexyl phoscompounds are set out in Table II. The percent control phoroamidothioate 5O reported is an average of the two and four week results.

Compound: g./qt. percent Ngll-dinethyl O-methyl S-ethyl phospholoamido- 0.01 92 we a.

N,N-dimetl1yl O.ethyl S-ethyl phosphoroamido thioate 0. O1 8 1 N,N-dimothyl O-isopropyl S-ethyl phosphoroamidothioate 0. 04 57 N-N-dimethyl O-methyl S-butyl posphoamidothioate 0.01 80 N-N-dimethyl O-ethyl S-cyolohexyl phosphorothioate O. 01 N,N-dietl1y1 O-methyl S-hexyl phosphoroamidothioate 0. 04 63 N,Ndiethyl O-mothyl S-cyclohexyl phosphoroamidothioate 0. O1 75 N,N-diisopr0pyl O-methyl S-butyl phosphoroamidothioate 0. 04 84 N,N-dial1yl O-methyl S-ethyl phosphoroamidothioate 0.01 75 N,N-dial1yl O-methyl S-butyl phosphoroamidot ioate 0. 04 96 N,N-diallyl O thyl nonyl phosphoroamidothioate 0. 04 50 N ,N,N, -tetramethyl S-ethyl phosphorodiamidot e 0.01 83 N,N,N,N-tetramethyl S-propyl phosphorodiamidothioate 0. 002 61 N,N,N,N-tetramethy1 S-butyl phosphorodiamidothloate 0. 001 80 N,N,N,N-tetramethyl S-cyclohexyl phosphorodiamidothioate 0. 01 87 N,N,N,N-tetraethyl S-butyl phosphorodiamidothioate 0. 01 S0 EXAMPLE V Other biological properties Insect t0xicity.-N,N,N,N tetramethyl S butyl phosphorodiamidothioate has been found to be residually toxic in the soil to rootworm larvae. 10 p.p.m. mixed into the soil killed 100 percent of the rootworms after 14 days. After 28 days, 100 percent of the larvae were controlled at a dosage of 30 ppm. mixed into the soil. This compound exhibits toxicity as well to a number of other insects, for example the pea aphid, mosquito larvae and the two-spotted spider mite.

Microbicide activity-Several of the phosphoroamidothioates of the invention were found active on a number of microorganisms in in vitro tests. For example, N,N,- diallyl O-methyl S-heptyl phosphoroamidothioate at 50 ppm. inhibited growth of nine species of microorganisms including bacteria, yeasts, and fungi.

Anthelmintic activity.1n laboratory tests N,N-diallyl O-ethyl S-cyclohexyl phosphoroamidothioate and N,N- diallyl Oethy1 S-propyl phosphoroamidothioate were effective in clearing mice of internal nematodes.

When used as agricultural pesticides the compounds used according to the invention may be formulated as liquids or as solid composition according to conventional methods known in the formulating art.

Liquid compositions containing up to 50% by weight of the desired amount of the active agent may be prepared by dissolving the chemical in an inert organic solvent such as xylene, acetone, isopropyl alcohol, carbon tetrachloride or the like. By the use of suitable emulsifying and dispersing agents these compounds (or phosphoroamiclo and diamidothioates) can be emulsified or dispersed in water and the emulsion applied to the soil to be treated to provide effective control of the nematodes or insects therein. Any of the usual emulsifying and dispersing agents commonly employed in forming aqueous emulsions and suspensions of water-insoluble materials can be used for this purpose. Generally but a small concentration of the emulsifying agent is required, as little as 0.05% of the weight of the final formulation being effective in many cases, while seldom will more than about 10% of the weight of the final formulation be required. Usually, the concentration of the emulsifying or dispersing agent will be from about 0.5 to about 5% of the weight of the formulation.

Solid formulations may be dusts, granules, or :wettable powders. The active ingredient content in the case of dusts or granules can vary from about 1% to about 10% by weight of the total formulation. Wettable powders may contain about 25% to about of the active ingredient on the same basis. Suitable diluents for agricultural solid formulations include clays such as the kaolinites and attapulgites, mineral diluents such as talc, pyrophyllite and chemically modified minerals such as precipitated calcium carbonate to mention a few. Wettable powder formulations contain in addition wetting, sticking and/or suspending agents.

The quantity of active ingredient used per acre will depend upon the particular nematode pest controlled. Generally dosages within the range of one pound to twenty pounds per acre will give control of nematodes in the soil.

A phosphoroamidothioate or phosphorodiamidothioate of the invention may be the sole active ingredient in a formulation, more than one such compound may be employed, or such a compound or compounds may be blended with other pesticides.

We claim as our invention:

1. The method of controlling nematodes which attack plants which comprises contacting said nematodes with a pesticidally effective amount of a compound of the formula:

(011 wherein R, R and R each independently represent a member selected from the group consisting of alkyl, alkenyl, chloroalkyl and bromoalkyl of 1 to 12 carbon atoms; R =R, R .R and cycloalkyl and alkynyl of up to 12 carbon atoms; m=2 \when n=0 and m=1 when 11:1.

2. The method of claim 1 wherein m=2 and n=0.

3. The method of claim 2 wherein R and R represent alkyl of 1 to 4 carbon atoms.

4. The method of claim 2 wherein the nematocidal compound is N,N,N,N-tetramethyl S-butyl phosphorodiamidothioate.

References Cited FOREIGN PATENTS 63,176 2/1961 Australia. 1,142,866 1/1963 Germany.

STANLEY J. FRIEDMAN, Primary Examiner.

U.S. Cl. X.R. 4242l9 

